Our overall objective is understanding the molecular mechanisms associated with the drug-induced effects on hemoglobin and red cells. Several of our physical-chemical studies have indicated a possible relationship between observations made on a molecular level and those made clinically. We have studied the interaction of phenylhydrazine and menadione with hemoglobin. We have observed the generation of superoxide anions in each reaction. Superoxide anions are formed by the univalent reduction of oxygen and are potentially toxic to the red cell. We have also exposed red cells to a superoxide anion source and have shown that these free radical anions cause hemoglobin breakdown and hypotonic lysis. We shal direct our research efforts toward unraveling the mechanism by which drugs produce hemoglobin breakdown and hemolysis, with specific emphasis on the role that the superoxide anion plays in these processes. Much of the proposed research has particular relevance to pharmacology, toxicology, and hematology.